A gene is considered a candidate gene for type 2 diabetes in Pima Indians if 1) it has a known physiological function in a pathway relevant to type 2 diabetes/obesity or 2) it is associated with diabetes/obesity in another human population or in an animal model. Candidate genes analyzed in the past year include: MCR4, FAS, PYY, Y2R, HNF4alpha, SUR, KIR6.2, LEPR, LEP, POMC, GRL, NPY, ADRB3, MC3R, GHRL and AGRP. Poymorphisms were identified in all of these genes and analyzed for association with type 2 diabetes, obesity, or metabolic traits that predict these diseases. Although none of these genes appear to have a significant role in determining type 2 diabetes or obsity in Pima Indians, we did observe some minor associations. For example, multiple variants in the HNF4alpha gene have ben reported to be associated with type 2 diabetes in a Finnish study population and the Ashkenazi Jewish population. Analysis of these variants in Pima Indians identified one variant that was also associated with type 2 diabetes, and two additional variants were associated wth insulin resitance, in this Native American population. In addition, analysis of the PYY and Y2R genes identified modest associations between genetic variations and severe obesity in male Pima Indians.